Creating universal blood-type organs for transplant
New proof-of-concept study reveals a way to make `universal' organs that
could be used in all recipients regardless of blood type

Date:
February 16, 2022
Source:
University Health Network
Summary:
A study has proved that it is possible to convert blood type
safely in donor organs intended for transplantation. This finding
is an important step towards creating universal type O organs,
which would significantly improve fairness in organ allocation
and decrease mortality for patients in the waitlist.



FULL STORY ==========================================================================
A study published in Science Translational Medicine performed at the
Latner Thoracic Surgery Research Laboratories and UHN's Ajmera Transplant Centre has proved that it is possible to convert blood type safely in
donor organs intended for transplantation. This finding is an important
step towards creating universal type O organs, which would significantly improve fairness in organ allocation and decrease mortality for patients
in the waitlist.


========================================================================== "With the current matching system, wait times can be considerably longer
for patients who need a transplant depending on their blood type,"
explains Dr.

Marcelo Cypel, Surgical Director of the Ajmera Transplant Centre and
the senior author of the study.

"Having universal organs means we could eliminate the blood-matching
barrier and prioritize patients by medical urgency, saving more lives
and wasting less organs," adds Dr. Cypel, who is also a Thoracic Surgeon
at UHN's Sprott Department of Surgery, a Professor in the Department of
Surgery at U of T and the Canada Research Chair in Lung Transplantation.

Blood type is determined by the presence of antigens on the surface of
red blood cells -- type A blood has the A antigen, B has the B antigen,
AB blood has both antigens and O has none. Antigens can trigger an
immune response if they are foreign to our bodies. That is why for blood transfusions we can only receive blood from donors with the same blood
type as ours, or universal type O.

Likewise, antigens A and B are present on the surfaces of blood vessels
in the body, including vessels in solid organs. If someone who is type O (meaning they have anti-A and anti-B antibodies in their blood stream)
received an organ from a type A donor, for example, the organ in all
likelihood would be rejected.

Consequently, donor organs are matched to potential recipients in the
waitlist based on blood type, among other criteria.

Patients who are type O wait on average twice as long to receive a lung transplant compared to patients who are type A, explains Dr. Aizhou Wang, Scientific Associate at Dr. Cypel's lab and first author of the study.



========================================================================== "This translates into mortality. Patients who are type O and need a lung transplant have a 20% higher risk of dying while waiting for a matched
organ to become available," says Dr. Wang.

This disparity is also present for other organs, she adds, where a patient
who is type O or B in need of a kidney transplant will be on the waitlist
for an average of 4 to 5 years, compared to 2 to3 years for types A or AB.

"If you convert all organs to universal type O, you can eliminate
that barrier completely." The experiment This proof-of-concept study
was done at Dr. Cypel's research lab, part of Latner Thoracic Surgery
Research Laboratories. The experiment used the Ex Vivo Lung Perfusion
(EVLP) System pioneered in Toronto as a platform for the treatment. The
EVLP system pumps nourishing fluids through organs, enabling them to be
warmed to body temperature, so that they can be repaired and improved
before transplantation.



========================================================================== Human donor lungs not suitable for transplantation from type A donors were
put in the EVLP circuit. One lung was treated with a group of enzymes to
clear the antigens from the surface of the organ, while the other lung,
from the same donor, remained untreated.

The team then tested each of the lungs by adding type O blood (with high concentrations of anti-A antibodies) to the circuit, to simulate an ABO incompatible transplant. The results demonstrated that the treated lungs
were well tolerated while the untreated ones showed signs of rejection.

Gut enzymes key to creating universal organs This study was successful
because of important interdisciplinary efforts across multiple
organizations in Canada, including UHN, University of Toronto, University
of British Columbia and University of Alberta.

"By exchanging ideas across disciplines and across the country, we
became one collaborative effort to tackle an important problem in organ transplantation," says Dr. Wang.

UBC biochemist Dr. Stephen Withers and his team found a group of enzymes
in 2018, which was key to this first step in creating universal blood-type organs.

These enzymes were delivered to the lungs in this study using the EVLP
circuit.

"Enzymes are Mother Nature's catalysts and they carry out particular
reactions.

This group of enzymes that we found in the human gut can cut sugars from
the A and B antigens on red blood cells, converting them into universal
type O cells.

"In this experiment, this opened a gateway to create universal blood-type organs," explains Dr. Withers.

"This is a great partnership with UHN and I was amazed to learn about the
ex vivo perfusion system and its impact for transplants. It is exciting to
see our findings being translated to clinical research," adds Dr. Withers.

As next step, the team of researchers is working on a proposal for a
clinical trial within the next 12 to 18 months.

========================================================================== Story Source: Materials provided by University_Health_Network. Note:
Content may be edited for style and length.


========================================================================== Journal Reference:
1. Aizhou Wang, Rafaela V. P. Ribeiro, Aadil Ali, Edson Brambate,
Etienne
Abdelnour-Berchtold, Vinicius Michaelsen, Yu Zhang, Peter Rahfeld,
Haisle Moon, Hemant Gokhale, Anajara Gazzalle, Prodipto Pal,
Mingyao Liu, Thomas K. Waddell, Christine Cserti-Gazdewich,
Kathryn Tinckam, Jayachandran N.

Kizhakkedathu, Lori West, Shaf Keshavjee, Stephen G. Withers,
Marcelo Cypel. Ex vivo enzymatic treatment converts blood type A
donor lungs into universal blood type lungs. Science Translational
Medicine, 2022; 14 (632) DOI: 10.1126/scitranslmed.abm7190 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/02/220216140411.htm

--- up 10 weeks, 4 days, 7 hours, 13 minutes
* Origin: -=> Castle Rock BBS <=- Now Husky HPT Powered! (1:317/3)